Indocyanine Green Angiographic Findings of Obscure Choroidal Abnormalities in Neurofibromatosis

Korean J Ophthalmol 2012;26(3):230-234 http://dx.doi.org/10.3341/kjo.2012.26.3.230 pISSN: 1011-8942 eISSN: 2092-9382

Case Report Indocyanine Green Angiographic Findings of Obscure Choroidal Abnormalities in Neurofibromatosis

Yong Soo Byun, Young Hoon Park Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea

We report two cases of choroidal neurofibromatosis, detected with the aid of indocyanine green angiography (ICGA) in patients with neurofibromatosis (NF)-1, otherwise having obscure findings based on ophthalmoscopy and fluoresceine angiography (FA). In case 1, the ophthalmoscopic exam showed diffuse bright or yellowish patched areas with irregular and blunt borders at the posterior pole. The FA showed multiple hyperfluorescent areas at the posterior pole in the early phase, which then showed more hyperfluorescence without leakage or extent in the late phase. The ICGA showed diffuse hypofluorescent areas in both the early and late phases, and the deep choroidal vessels were also visible. In case 2, the fundus showed no abnormal findings, and the FA showed weakly hypofluorescent areas with indefinite borders in both eyes. With the ICGA, these areas were more hypofluorescent and had clear borders. Choroidal involvement in NF-1 seems to occur more than expect- ed. In selected cases, ICGA is a useful tool to be utilized when an ocular examination is conducted in a patient that has no definite findings based on the ophthalmoscope, B-scan, or FA tests.

Key Words: Choroid, Choroidal neurofibroma, Indocyanine green angiography, Neurofibromatoses

Neurofibromatosis (NF) consists of at least two geneti- [2,4]. cally distinct disorders: NF-1 (von Recklinghausen’s or NF can involve multiple organs, and the ocular manifes- peripheral neurofibromatosis) and NF-2, which is formerly tations of NF-1 include multiple iris hamartomas (Lisch known as central neurofibromatosis [1-3]. NF-1, first ob- nodules), congenital glaucoma, optic nerve gliomas, plexi- served by von Recklinghausen, manifests clinically in form neurofibromas of the eyelids, and uveal hamartomas. infancy with multiple cafe-au-lait skin spots, intertriginous On the other hand, retinal or choroidal lesions are rarely freckling, iris hamartomas (Lisch nodules) and multiple involved in the patients with NF-1 [5-8]. Furthermore, NF-1 cutaneous neurofibromas and is caused by genetic ab- patients tend to not undergo detailed ophthalmic examina- normalities on chromosome 17. NF-2 is characterized by tions since NF-1 is rarely a vision-threatening disorder. In bilateral vestibular schwannomas (acoustic neuromas) this study, we report two cases of choroidal abnormalities and brain and spinal cord tumors, and it is transmitted by occurring in NF patients which were detected by fluores- genetic abnormalities on chromosome 22. The prevalence ceine angiography (FA) and indocyanine green angiogra- of NF-1 is approximately 1 in 2,500 to 3,300 individuals, phy (ICGA) in patients with NF-1 that had obscure fundus while NF-2 is observed in approximately 1 in 50,000 to findings but good vision. 120,000 individuals, regardless of race, sex, or ethnicity Case Reports Received: May 11, 2010 Accepted: October 11, 2010 Case 1

Corresponding Author: Young Hoon Park, MD, PhD. Department of The following is a case of a 59-year-old female who had Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, #222 Banpo-daero, previously been diagnosed with NF type 1. She was re- Seocho-gu, Seoul 137-701, Korea. Tel: 82-2-2258-6201, Fax: 82-82-2-599- ferred to the Retina Clinic at Uijeongbu St. Mary’s Hospi- 7405, E-mail: [email protected] tal with the complaint of blurred vision for several months.

© 2012 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses /by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

230 YS Byun, et al. ICG Findings of Choroidal Neurofibromatosis

Diagnosis was confirmed at the age of 55 years, and both up visit, the fundoscopic exam showed diffuse bright or her mother and sister had the same disease. Upon ocular yellowish patched areas with irregular and blunt borders examination, she had multiple iris hamartomas (Lisch nod- at the posterior pole. Although alterations were not clearly ule), and intraocular lenses with posterior capsular opacity visible by fundoscopy, there was a slightly patched pattern in both eyes. The patient had cataract surgeries in both or an uneven surface on the posterior pole (Fig. 1A). The eyes 2 years prior to our examination. Her visual acuity FA showed multiple hyperfluorescent areas at the posterior was 20 / 120 in the right eye and 20 / 60 in the left eye at pole in the early phase, and then these areas showed more the time of her initial visit. After laser capsulotomy, the vi- hyperfluorescence without leakage and were extent in the sion in both of her eyes improved to 20 / 20. At the follow- late phase (Fig. 1B and 1C). These areas corresponded to

A B

C D

Fig. 1. Case 1. Diffuse bright or yellowish patched areas with irregular and blunt borders at the posterior pole (A). Early-phase fluorescein angiography of the same eye shows several hyperfluorescent areas at the posterior pole, and these areas correspond to the bright patched areas that are seen in fundoscopy. These represent the zones of retinal pigmented epithelium alterations. These areas appear more hyperfluorescent with the same extent in the late phase (B,C). Indocyanine green angiography showed diffuse hypofluorescent areas in both the early and late phases, and the deep choroidal vessels are visible within the hypofluorescent area (D,E).

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the multiple yellowish patched lesions that were invisible ophthalmological examination. The patient had no relatives in fundoscopy. The ICGA showed diffuse hypofluorescent with the same disease and had multiple cutaneous neurofi- areas in both the early and late phase, and the deep choroi- bromas over the body, although these were only systemic dal vessels were visible (Fig. 1D and 1E) manifestations. Visual acuity was 1.0 in both eyes, and the microscopic examination showed Lisch nodules in both Case 2 eyes. The fundus and FA showed no definite abnormalities in either eye (Fig. 2A-2D). However, the ICGA showed An 11-year-old male patient with NF-1 was referred to multiple hypofluorescent areas with clear borders in the the Retina Clinic at Uijeongbu St. Mary’s Hospital for an early phase, which remained small or disappeared com-

A B

C D

Fig. 2. Case 2. Normal fundus was observed (A). Fluoresceine angiography showed hypofluorescent areas with blurred demarcation (B-D). Indocyanine green angiography (ICGA) showed multiple hypofluorescent areas with clear borders in the early phase, which remained small in the late phase. The multiple neurofibromas occupying the choroid are able to be detected by the ICGA, but these lesions had not yet led to retinal pigmented epithelium abnormalities (E).

232 YS Byun, et al. ICG Findings of Choroidal Neurofibromatosis

RPE and cause its eventual atrophy (yellowish patches on pletely in the late phase (Fig. 2E). ophthalmoscopy that correspond to the hyperfluorescent areas in the FA). Discussion In our case 1, the fundus did not show yellowish nodules Many studies have reported ocular manifestations in but rather bright patched areas around the posterior pole, NF-1 patients, including choroidal abnormalities [9-16]. similar to Yasunari’s cases. These lesions appeared to be However, most of these cases are included in histopatho- hyperfluorescent areas in the FA, which suggests RPE logic studies or have abnormalities that are definitely alterations are present. However, the ICGA showed dif- observable with the fundoscope. Choroidal neurofibroma- fuse hypofluorescence with visible deep choroidal vessels tosis is thought to be a rare form of neurofibromatosis that from the early phase to the late phase and was unrelated affects the eyes [9,10,14-16]. The actual prevalence of this to the lesion observed by both fundoscopy and FA. This disorder may be higher than currently believed because finding is believed to be due to the diffuse scattering of patients with good vision tend not to undergo ocular ex- the neurofibromatose tissue in the choroid without re- aminations. Thus, without an ocular examination, which markable prominence. In regard to case 2, the abnormal usually involves a conventional ophthalmoscopic exami- alterations were not clearly visible by either fundoscopy nation or FA, patients with good vision are not tested for or FA. However, the ICGA showed multiple hypofluores- choroidal abnormalities. In some patients, the choroid cent areas that persisted into the late phase. It is thought neurofibromatosis may appear as yellowish nodules, but that multiple neurofibromas occupying the choroid were these may appear as bright patched areas upon fundo- detected by the ICGA, and that these neurofibromas were scopic examination in only weakly affected patients. FA not yet producing RPE abnormalities. However, it is insuf- shows irregular hyperfluorescence that is related to retinal ficient to conclude that these abnormalities presented with pigmented epithelium (RPE) alteration, but it is not able to choroidal neurofibromas because various possibilities exist detect underlying choroidal abnormalities. for the underlying cause. Choroidal involvement in NF-1 ICGA has overcome the limitations of FA in regard to may occur more often than what is currently believed. imaging of the choroidal structure [17-20]. Several au- Also, the underlying cause of this, whether it be due to thors have previously reported the presence of choroidal the space-occupying neurofibroma itself or the vascular neurofibromatosis with the use of ICGA. Yasunari et al. change associated with the neurofibromatosis, may lead to [21] have reported that they were able to detect choroidal the hypoperfusion of the lesion that would later result in abnormalities in all 17 of their patients with NF-1 using RPE alteration. We believe that these ICGA patterns that scanning laser ophthalmoscopy (SLO) and ICGA, and that are seen in our cases may not be due to hypoperfusion or the choroid was one of the structures most commonly af- nonperfusion of the choroidal lobules, but due instead to fected by NF-1. They suggested that the hypofluorescent blocked fluorescence by the choroid-occupying materials. areas on the ICGA, that appeared to be obscure with SLO In conclusion, these two cases have shown that choroidal and FA in their less affected patients, were probably not abnormalities occur more often than currently believed in caused by disturbance of the choriocapillaris circulation, patients with NF-1. Fundoscopic examination can identify but rather by the presence of refractile tissue or material grossly proliferative neurofibromatosis but only in the later in the choroid. They believed that such refractile material stages, and FA can only describe actual RPE alterations, presumably blocks the fluorescence from the underlying secondary to choriocapillaris nonperfusion. However, choroidal vessels and produces a hypofluorescent appear- ICGA is a useful tool to detect the early changes that occur ance which disappears on the ICGA at the late phase due with choroid abnormalities. Although no abnormal finding to the indocyanine-green dye being extravasated into the was found by either fundoscopy or FA, ICGA seems to be choroidal stroma. In contrast, Rescaldani et al. [10] have useful for ocular examinations of NF-1 patients that have suggested in their study that the early hypofluorescent good vision. areas in the ICGA are due to the hypo- or non-perfused lobules of the choriocapillaris rather than the blocking of fluorescent light by the neurofibromatose choroidal nod- Conflict of Interest ules since these areas became smaller or disappeared in the No potential conflict of interest relevant to this article late phase and because the deep choroidal vessels were vis- was reported. ible within these areas. Additionally, one histological study has documented that Schwann cell growth with dysplasia of the smooth muscle cells of the arteriolar wall leads to References the gradual narrowing of the vessel lumen [22]. Accord- 1. Von Recklinghausen FD. Ueber die multiplen Fibrome ing to Rescaldani et al. [10], chronic hypoperfusion of the der Haut und ihre Beziehung zu den multiplen Neuromen. choriocapillaris appears to cause lesions to the overlying Festschrift zur Feier des fünfundzwanzigjährigen Beste-

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